Ssh2, also known as Slingshot phosphatase 2, is an important regulator of actin remodeling. It is involved in the cofilin-mediated actin remodeling pathway and plays a crucial role in multiple biological processes [1,2]. It is essential for male fertility as it is required for acrosome biogenesis during spermatogenesis in mice [1].

In Ssh2 knockout (KO) mice, spermatogenesis was arrested at the early spermatid stage with increased apoptotic index. The acrosome biogenesis was impaired, characterized by defective transport/fusion of proacrosomal vesicles. Also, disorganized F-actin structures accompanied by excessive phosphorylation of COFILIN were observed in the testes [1]. In human carcinoma cell lines with the loss of the Birt-Hogg-Dubé tumour suppressor gene (FLCN), knockdown of SSH2 induced Caspase3/7 activation in a dose-dependent manner, suggesting SSH2 as a potential therapeutic target for BHD syndrome and related tumors [2].

In conclusion, Ssh2 is essential for acrosome biogenesis and male fertility through its role in actin remodeling. The study of Ssh2 KO mouse models has provided insights into its function in spermatogenesis and its potential as a therapeutic target in certain cancers related to FLCN deficiency.

References:

1. Xu, Ke, Su, Xianwei, Fang, Kailun, Chen, Zi-Jiang, Liu, Hongbin. 2023. The Slingshot phosphatase 2 is required for acrosome biogenesis during spermatogenesis in mice. In eLife, 12, . doi:10.7554/eLife.83129. https://pubmed.ncbi.nlm.nih.gov/36942942/

2. Lu, X, Boora, U, Seabra, L, Nagy, Z, Maher, E R. 2013. Knockdown of Slingshot 2 (SSH2) serine phosphatase induces Caspase3 activation in human carcinoma cell lines with the loss of the Birt-Hogg-Dubé tumour suppressor gene (FLCN). In Oncogene, 33, 956-65. doi:10.1038/onc.2013.27. https://pubmed.ncbi.nlm.nih.gov/23416984/